Helicobacter pylori Infection and Risk of Chronic Obstructive Pulmonary Disease: A Meta-Analysis and Mendelian Randomization Study

Yunpeng Xu,1,* Junfen Li,1,* Cuifang He,1 Aiju Su,1 Hongbo Jiang,1 Boyan Ma,1 Lei Zhu,2 Zi Yang,3 Fanqi Wu,4 Jian Liu1,5 1The First Clinical Medical College of Lanzhou University, Lanzhou, People’s Republic of China; 2Department of ICU, The First Hospital of Lanzhou University, Lanzhou, People’s Republic of China; 3Information Center, The First Hospital of Lanzhou University, Lanzhou, People’s Republic of China; 4Department of Respiratory and Critical Care Medicine, The Second Hospital of Lanzhou University, Lanzhou, People’s Republic of China; 5Gansu Province Maternity and Child-Care Hospital (Gansu Provincial Central Hospital), Lanzhou, People’s Republic of China*These authors contributed equally to this workCorrespondence: Jian Liu, Email [email protected] Fanqi Wu, Email [email protected]: Helicobacter pylori (H. pylori) infection and chronic obstructive pulmonary disease (COPD) are both common global public health burdens. Current evidence suggests that H. pylori infection may be associated with the development and progression of COPD.Methods: This study conducted a meta-analysis to systematically evaluate the association between H. pylori infection and COPD risk. Eight Chinese and English databases were searched through September 2025. We then performed two-sample Mendelian randomization (MR) using genetic instruments for H. pylori antibody phenotypes and COPD GWAS summary statistics to test bidirectional causality.Results: A total of 27 studies were included, comprising 7159 participants. Compared with controls, COPD patients had a higher H. pylori positivity rate (RR = 1.43, 95% CI: 1.25– 1.60, P < 0.00001). Among COPD patients, H. pylori positivity was associated with poorer lung function (FEV1/FVC: MD = − 6.75, 95% CI: − 9.17 to − 4.34, P < 0.00001; FEV1%: MD = − 9.34, 95% CI: − 12.61 to − 6.07, P < 0.00001; FEV1: MD = − 0.16, 95% CI: − 0.23 to − 0.09, P < 0.00001; FVC%: MD = − 5.29, 95% CI: − 9.76 to − 0.81, P = 0.02; FVC: MD = − 0.15, 95% CI: − 0.28 to − 0.01, P = 0.03). Compared with patients with severe-to-very severe COPD, those with mild-to-moderate COPD had a lower prevalence of H. pylori infection (RR = 0.75, 95% CI: 0.59– 0.96; P = 0.02). However, the two-sample MR analysis did not find evidence of a bidirectional causal relationship between H. pylori antibodies and COPD.Conclusion: The study shows that H. pylori infection is more prevalent among patients with COPD and is associated with reduced lung function and greater disease severity, but no genetic evidence of causality was identified. Therefore, based on current evidence, routine H. pylori screening or eradication therapy is not recommended in the general COPD population.Keywords: pulmonary disease, chronic obstructive, Helicobacter pylori, evidence-based medicine, Mendelian randomization analysis